ACTL6B p.Glu48Asp
c.144G>C · rs141807780 · VCV1285116
Computational evidence
| Protein change | ||
| AlphaMissense | 0.0557 | likely benign |
|---|---|---|
| REVEL | 0.287 | benign-leaning |
| SaProt | LLR -7.08 | tolerated |
| ⇒ AlphaMissense, REVEL and SaProt all call this tolerated. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 1.4 | GERP -3.2, phastCons 1 |
| Regional constraint | o/e 0.69 | unconstrained · MANE · 9,273 bp · p 1.9e-09 · regional, not allelic |
| Overall | ||
| CADD | 19.07 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Finnishnot grpmax-eligible | 2.52% | 40 |
| European (non-Finnish)grpmax | 0.151% | 664 |
| Remaining individualsnot grpmax-eligible | 0.12% | 833 |
| Admixed American | 0.0317% | 3,159 |
| African / African-American | 0.024% | 4,171 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,578 |
| South Asian | 0.0011% | 91,060 |
Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- ACTL6B
- Protein
- p.Glu48Asp
- Coding
- c.144G>C
- MANE Select
- NM_016188
- dbSNP
- rs141807780
- Type
- single nucleotide variant
- Location
- chr7:100655545 (GRCh38)
- Gene constraint
- LOEUF 0.954 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 91.52
- Residue 48
- the 'essential for mediating its function in dendritic development; may contribute to neuronal-specific targeting' region
Similar variants
- ACTL6B p.Glu48= Likely benign ★ same residue
- ACTL6B p.Arg97Ter Likely pathogenic ★★ same type
- ACTL6B p.Gln186Ter Pathogenic/Likely pathogenic ★★ same type
- ACTL6B p.Gln278Ter Likely pathogenic ★★ same type
- ACTL6B p.Gly343Arg Pathogenic/Likely pathogenic ★★ same type
- ACTL6B p.Gly349Ser Likely pathogenic ★★ same type
- ACTL6B p.Trp247Ter Likely pathogenic ★★ same type
- ACTL6B p.Arg363Gln Uncertain significance ★★ ⚠ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/actl6b-p-glu48asp (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown